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Allopregnanolone modulates spontaneous GABA release via presynaptic Cl- permeability in rat preoptic nerve terminals
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Laboratory of Ionic Channels of Cell Membranes, Institute of Cytology, Russian Academy of Sciences, Russia.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
2002 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 958, no 2, 405-413 p.Article in journal (Refereed) Published
Abstract [en]

The endogenous neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) affects presynaptic nerve terminals and thereby increases the frequency of spontaneous GABA release. The present study aimed at clarifying the mechanisms underlying this presynaptic neurosteroid action, by recording the frequency of spontaneous GABA-mediated inhibitory postsynaptic currents (sIPSCs) in neurons from the medial preoptic nucleus (MPN) of rat. Acutely dissociated neurons with functional adhering nerve terminals were studied by perforated-patch recording under voltage-clamp conditions. It was shown that the sIPSC frequency increased with the external K(+) concentration ([K(+)](o)). Further, the effect of allopregnanolone on the sIPSC frequency was strongly dependent on [K(+)](o). In a [K(+)](o) of 5 mM, 2.0 microM allopregnanolone caused a clear increase in sIPSC frequency. However, the effect declined rapidly with increased [K(+)](o) and at high [K(+)](o) allopregnanolone reduced the sIPSC frequency. The effect of allopregnanolone was also strongly dependent on the external Cl(-) concentration ([Cl(-)](o)). In a reduced [Cl(-)](o) (40 mM, but with a standard [K(+)](o) of 5 mM), the effect on sIPSC frequency was larger than that in the standard [Cl(-)](o) of 146 mM. The dependence of the effect of allopregnanolone on [K(+)](o) and on estimated presynaptic membrane potential was also altered by the reduction in [Cl(-)](o). As in standard [Cl(-)](o), the effect in low [Cl(-)](o) declined when [K(+)](o) was raised, but reversed at a higher [K(+)](o). The GABA(A) receptor agonist muscimol also potentiated the sIPSC frequency. Altogether, the results suggest that allopregnanolone exerts its presynaptic effect by increasing the presynaptic Cl(-) permeability, most likely via GABA(A) receptors.

Place, publisher, year, edition, pages
Elsevier, 2002. Vol. 958, no 2, 405-413 p.
Keyword [en]
Excitable membranes and synaptic transmission, Presynaptic mechanisms, spontaneous GABA release, allopregnanolone, medial preoptic nucleus, patch clamp
National Category
Physiology Neurology
URN: urn:nbn:se:umu:diva-82530DOI: 10.1016/S0006-8993(02)03704-6ISI: 000180087300021PubMedID: 12470877OAI: diva2:661805

Article number: PII S0006-8993(02)03704-6

Available from: 2013-11-05 Created: 2013-11-05 Last updated: 2014-04-24Bibliographically approved

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Haage, DavidDruzin, MichaelJohansson, Staffan
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